Trifluoroacetic acid → HCID 178502321, compound

HRID 625570Notes

Reaction equation

HRID 625570 reaction equation
C(O)(C(F)(F)F)=O.[CH3:8][O:9][C:10]([NH:12][C@H:13]([C:17]([N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[C:24]1[NH:28][C:27]2[CH:29]=[CH:30][C:31]([C:33]3[CH:34]=[C:35]4[C:40](=[CH:41][CH:42]=3)[CH:39]=[C:38]([C:43]3[CH:63]=[CH:62][C:46]5[NH:47][C:48]([C@@H:50]6[CH2:54][CH2:53][CH2:52][N:51]6C(OC(C)(C)C)=O)=[N:49][C:45]=5[CH:44]=3)[CH:37]=[CH:36]4)=[CH:32][C:26]=2[N:25]=1)=[O:18])[CH:14]([CH3:16])[CH3:15])=[O:11]>C(Cl)Cl>[CH3:15][CH:14]([CH3:16])[C@H:13]([NH:12][C:10](=[O:11])[O:9][CH3:8])[C:17]([N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[C:24]1[NH:28][C:27]2[CH:29]=[CH:30][C:31]([C:33]3[CH:42]=[CH:41][C:40]4[C:35](=[CH:36][CH:37]=[C:38]([C:43]5[CH:63]=[CH:62][C:46]6[NH:47][C:48]([C@@H:50]7[CH2:54][CH2:53][CH2:52][NH:51]7)=[N:49][C:45]=6[CH:44]=5)[CH:39]=4)[CH:34]=3)=[CH:32][C:26]=2[N:25]=1)=[O:18]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 178502320HCID 178502320, compound

Product 1

HCID 178502321HCID 178502321, compoundYield 71.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of a TFA salt of tert-butyl (2S)-2-(5-(6-(2-((2S)-1-(N-(methoxycarbonyl)-L-valyl)-2-pyrrolidinyl)-1H-benzimidazol-5-yl)-2-naphthyl)-1H-benzimidazol-2-yl)-1-pyrrolidinecarboxylate (445 mg) in DCM (10 mL) at room temp was added TFA (1 mL, 13 mmol). The mixture was stirred at rt for 3 h, concentrated, and the residue was diluted in MeOH, loaded onto a Strata XC MCX cartridge and washed with methanol. The compound was release from the cartridge by eluting with a solution of 2M ammonia in methanol and then evaporated under reduced pressure to give methyl ((1S)-2-methyl-1-(((2S)-2-(5-(6-(2-((2S)-2-pyrrolidinyl)-1H-benzimidazol-5-yl)-2-naphthyl)-1H-benzimidazol-2-yl)-1-pyrrolidinyl)carbonyl)propyl)carbamate (275 mg) as orange solid LC-MS retention time 1.120 min; m/z 656.27 [M+H]+. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 3 min, a hold time of 1 min and an analysis time of 4 min where Solvent A was 10% acetonitrile/90% water/0.1% TFA and Solvent B was 90% acetonitrile/10% water/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (500 MHz, MeOD) δ ppm 8.26 (br s, 1H), 8.22 (br s, 1H), 8.08-8.16 (m, 3H), 8.04-8.08 (m, 1H), 8.03 (s, 1H), 7.86-7.96 (m, 3H), 7.73-7.82 (m, 2H), 5.88-5.93 (m, 0.1H), 5.37-5.44 (m, 0.9H), 5.07-5.15 (m, 1H), 4.28-4.33 (m, 1H), 4.12-4.19 (m, 0.8H), 4.06-4.10 (m, 0.2H), 3.94-4.02 (m, 1H), 3.59-3.75 (m, 4H), 3.50-3.59 (m, 1H), 2.63-2.74 (m, 2H), 2.41-2.47 (m, 1H), 2.23-2.40 (m, 5H), 2.06-2.16 (m, 1H), 1.00-1.04 (m, 0.4H), 0.94-1.00 (m, 3H), 0.88-0.93 (m, 2.6H).

Workup

  1. concentrationconcentrated
  2. additionthe residue was diluted in MeOH
  3. washwashed with methanol
  4. washby eluting with a solution of 2M ammonia in methanol
  5. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-d95757bab96146db97e675a6591cb92e
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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